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Expression of HER2 and Mismatch Repair Proteins in Surgically Resected Gallbladder Adenocarcinoma

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Abstract
Background Gallbladder cancer (GBC) has a poor prognosis. Although complete surgical resection is the only successful approach for improving survival, additional therapeutic modalities are required for recurrent or surgically unresectable GBCs.

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Materials and Methods To determine the expression status of HER2 and the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2, immunohistochemical staining of MMR proteins and HER2 was carried out in 216 surgically resected GBCs. HER2 labeling was scored by adopting a scoring system for gastric carcinomas. Tissues scoring 0 to 2+ were defined as HER2 negative, whereas those scoring 3+ were regarded as HER2-positive. In addition, silver in situ hybridization and microsatellite instability (MSI) analysis were conducted to confirm HER2 amplification and MSI, respectively.

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Results Three of 216 GBCs (1.3%) showed MMR protein deficiency. All three observed MSI cases exhibited dual loss of MSH2 and MSH6 protein expression. However, no cases showed loss of either MLH1 or PMS2 expression. No association was observed between MMR protein deficiency and other clinicopathological factors. HER2 amplification was noted in 30 (13.9%) GBCs and associated with Crohn-like lymphoid reaction (P = 0.023). No survival difference was observed based on HER2 overexpression or HER2 amplification status.

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Conclusion MMR protein deficiency and HER2 overexpression were observed in a small subset (1.3% and 13.9%, respectively) of GBCs without simultaneous occurrence of deficient MMR protein expression and HER2 overexpression. The presence of Crohn-like lymphoid reaction may help identify cases with HER2 amplification, by using hematoxylin-stained slides. Although the proportion of MMR protein-deficient- and HER2-overexpressing GBCs was small, applying immunotherapy to MMR protein-deficient GBCs and herceptin to HER2-overexpressing GBCs may provide alternative treatment options for patients with GBC.
Author(s)
김규표김성주성유나유창훈이상수이재훈전선영홍승모황대욱황신
Issued Date
2021
Type
Article
Keyword
cancergallbladderHER2microsatellite Instabilitymismatch repair proteins
DOI
10.3389/fonc.2021.658564
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8158
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_d591750419c2493a8afede64cfd0740b&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Expression%20of%20HER2%20and%20Mismatch%20Repair%20Proteins%20in%20Surgically%20Resected%20Gallbladder%20Adenocarcinoma&offset=0&pcAvailability=true
Publisher
FRONTIERS IN ONCOLOGY
Location
스위스
Language
한국어
ISSN
2234-943X
Citation Volume
11
Citation Number
11
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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